Despite the wide body of literature dedicated to the investigation of adolescent sexual behavior, our understanding of the processes linking sexual risk behavior with its predictors and consequences remains limited. Previous research has identified numerous risk factors associated with early sexual risk behavior, such as early substance use, psychological distress, and early physical maturation. Sexual risk behavior, particularly during early adolescence, also increases an individual's risk of various negative physical outcomes, and some studies suggest that early, risky sexual behavior may be associated with later psychopathology, including increased substance use and depression. However, adolescents do not engage in these behaviors completely at random, and it is possible that confounding genetic and environmental factors could explain the associations between putative risk factors, sexual risk behavior, and subsequent negative outcomes. Most research on sexual risk behavior has relied on traditional family studies, which compare individuals from different families. Because these studies have not been able to account for unmeasured genetic and environmental influences shared by individuals within the same family that may differ between families, the research may be emphasizing spurious predictive associations between risk factors, sexual behavior, and later health outcomes. To address this limitation, the proposed study will utilize quasi-experimental designs (co-twin control and sibling comparisons) that can help tease apart the relative influence of genetic and environmental factors. Analyses will pull from two genetically informed datasets-twin pairs from the Study of Twin Adults: Genes and Environment in Sweden (N = 25,378) and sibling pairs from the Children of the National Longitudinal Survey of Youth in the United States (N = 6,056)-to increase understanding of the etiological mechanisms responsible for the associations between risky sexual behavior and its predictors and consequences. Specifically, analyses will examine whether twin and sibling pairs discordant for a hypothesized risk factor, such as substance use, also differ in their level of sexual risk behavior once shared genetic and environmental factors are considered. Analyses will also test whether twin and sibling pairs who differ in their age at first intercourse vary with regard to hypothesized consequences after controlling for these selection effects. Using these two datasets will provide an opportunity to find converging evidence from multiple studies and explore cross-cultural differences. While traditional research methods have identified statistical associations between putative risks and consequences of sexual risk behavior, the quasi-experimental, genetically sensitive design of the proposed study will provide more stringent tests of the causal process underlying these relations, as this theoretical approach has rarely been used in the examination of sexual risk behavior and associated problem behaviors. Increasing scientific knowledge in this area and better identifying modifiable target behaviors for risk prevention will have significant implications for sexual health prevention efforts and public policy initiatives. PUBLIC HEALTH RELEVANCE: Previous research has identified numerous risk factors and consequences associated with sexual risk behavior in adolescence, including substance use and psychological distress. Leaders in the field of public health have targeted reduction of sexual risk behaviors as a national priority in health research, but effective reduction of these behaviors requires that we identify those factors that are linked with sexual risk behavior through causal processes and may therefore be modified to reduce sexual risk behavior. The use of novel theoretical and analytical approaches in this area to better identify modifiable target behaviors for risk prevention will have significant benefits for sexual health prevention efforts.